title: Efficacy and safety of new oral anticoagulants for extended treatment of venous thromboembolism: systematic review and meta-analyses of randomized controlled trials.
abstract: BACKGROUND
  Currently available anticoagulants have limitations for long term treatment of venous thromboembolism (VTE).
  
  
  OBJECTIVE
  A meta-analysis was performed to evaluate the efficacy and safety of new oral anticoagulants (NOACs) for extended treatment of VTE.
  
  
  METHODS
  PubMed, Cochrane Library, EMBASE, Web of Science and CINAHL databases were searched from January 01, 2001 through February 28, 2013. Randomized controlled trials (RCTs) comparing NOACs (apixaban, rivaroxaban and dabigatran) with placebo or warfarin for extended treatment of VTE were selected. Primary efficacy outcome was recurrent VTE or VTE related death, and primary safety outcome was major bleeding. We used random-effects models.
  
  
  RESULTS
  Four RCTs included 7,877 participants. NOACs significantly lowered the risk of recurrent VTE or VTE-related death compared to placebo/warfarin (odds ratio [OR] 0.25, 95 % confidence interval [CI] 0.07 to 0.86; number needed to treat [NNT] = 30). All-cause mortality was significantly lower in NOACs group compared to placebo (OR 0.38, 95 % CI 0.18 to 0.80). Risk of major bleeding was not different with NOACs compared to placebo/warfarin (OR 0.88, 95 % CI 0.27 to 2.91). However, NOACs caused significantly higher rate of major or clinically relevant bleeding compared to placebo (OR 2.69, 95 % CI 1.25 to 5.77; number needed to harm [NNH] = 39). All three NOACs (apixaban, rivaroxaban and dabigatran) individually significantly reduced recurrent VTE or VTE-related death compared to placebo. Major or clinically relevant bleeding was higher with dabigatran and rivaroxaban but not with apixaban.
  
  
  CONCLUSIONS
  NOACs are effective for the extended treatment of venous thromboembolism and may reduce the risk of all-cause mortality. Dabigatran and rivaroxaban may cause more major or clinically relevant bleeding.
authors.affiliation: Department of Medicine, New York Medical College-Metropolitan Hospital Center, 1901 First Avenue, New York, NY, USA. parthasardarmd@gmail.com
authors.forename: Partha
authors.initials: P
authors.lastname: Sardar
authors.forename: Saurav
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukherjee
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants